The kidney is a structurally complex organ that has evolved to perform a number of important functions: e.g., excretion of the waste products of metabolism, regulation of body water and salt, maintenance of appropriate acid balance, and secretion of a variety of hormones and autocoids. Diseases of the kidney are as complex as its structure, but their study is facilitated by dividing them into those that affect four basic morphologic components: i.e., glomeruli, tubules, interstitium, and blood vessels. This traditional approach is useful because the early manifestations of diseases that affect each of these components tend to be distinctive. Further, some components appear to be more vulnerable to specific forms of renal injury. For example, glomerular diseases are often immunologically mediated, whereas tubular and interstitial disorders are more likely to be caused by toxic or infectious agents. Nevertheless, some disorders affect more than one structure. In addition, the anatomic interdependence of structures in the kidney implies that damage to one almost always secondarily affects the others. Thus, severe glomerular damage impairs flow through the peritubular vascular system; conversely, tubular destruction, by increasing intraglomerular pressure, may induce glomerular atrophy. Thus, whatever the origin, there is a tendency for all forms of chronic renal disease ultimately to destroy all four components of the kidney, culminating in chronic renal failure and what has been called end-stage contracted kidneys (Cotran et al., Basic Pathology, Sixth Edition, 1997).
Chemotherapy and immunosuppressive therapy refers to the use of cytotoxic or immunosuppressive agents such as, but not limited to, cyclophosphamide, doxorubicin, daunorubicin, vinblastine, vincristine, bleomycin, etoposide, topotecan, irinotecan, taxotere, taxol, 5-fluorouracil, methotrexate, gemcitabine, cisplatin, carboplatin, or chlorambucil, and cyclosporin A, tacrolimus, rapamycin, or corticosteroids to treat cancer patients or to inhibit graft rejection in transplant patients. Despite their efficacies, these agents are non-specific and, particularly at high doses, they are toxic to normal and rapidly dividing cells. Furthermore, their use may be limited by inherent untoward effects, of which acute myelosuppression, nephrotoxicity, cardiotoxicity, neurotoxicity, gastrointestinal, bladder, and pulmonary toxicities may worsen patient outcome over long time periods.
In autoimmune diseases such as diabetes mellitus, the kidneys are prime targets to suffer tissue damage or lesions. Three important lesions are encountered: (1) glomerular lesions; (2) renal vascular lesions, principally arteriolosclerosis; and (3) pyelonephritis, including necrotizing papillitis. Nephrectomy, or kidney removal, can also lead to renal dysfunction. Nephrectomy is performed on patients with cancer of the kidney (i.e., renal cell carcinoma); polycystic kidney disease in which sac-like structures displace healthy tissue; and serious infection of the kidney. It is also used to remove a healthy kidney from a donor for the purpose of kidney transplantation. Because the kidney is responsible for filtering wastes and fluid from the bloodstream, kidney function is critical to life. Nephrectomy candidates suffering from serious kidney disease, cancer, or infection usually have few treatment choices but to undergo the procedure. But if function is lost in the remaining kidney, the patient will require chronic dialysis treatments or transplantation of a healthy kidney to sustain life. Therefore, there exists a need for drugs with a good safety profile which can be administered to patients with kidney disease which can prolong kidney health or protect it from deterioration to the extent that the kidney can no longer function.